Selective organ cooling catheter and method of using the same

ABSTRACT

A heat transfer device has first and second elongated, articulated segments, each having a turbulence-inducing exterior surface. A flexible joint connects the first and second elongated, articulated segments. An inner coaxial lumen is disposed within the first and second elongated, articulated segments. The inner coaxial lumen is capable of transporting a pressurized working fluid to a distal end of the first elongated, articulated segment.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a continuation-in-part patent application of U.S. patentapplication Ser. No. 09/047,012, filed on Mar. 24, 1998, now U.S. Pat.No. 5,957,963 and entitled "Improved Selective Organ Hypothermia Methodand Apparatus", which is a continuation-in-part patent application ofco-pending U.S. patent application Ser. No. 09/012,287, filed on Jan.23, 1998, and entitled "Selective Organ Hypothermia Method andApparatus".

BACKGROUND OF THE INVENTION

I. Field of the Invention

The present invention relates generally to the modification and controlof the temperature of a selected body organ. More particularly, theinvention relates to a method and intravascular apparatus forcontrolling organ temperature.

II. Description of the Related Art

Organs in the human body, such as the brain, kidney and heart, aremaintained at a constant temperature of approximately 37° C. Hypothermiacan be clinically defined as a core body temperature of 35° C. or less.Hypothermia is sometimes characterized further according to itsseverity. A body core temperature in the range of 33° C. to 35° C. isdescribed as mild hypothermia. A body temperature of 28° C. to 32° C. isdescribed as moderate hypothermia. A body core temperature in the rangeof 24° C. to 28° C. is described as severe hypothermia.

Hypothermia is uniquely effective in reducing brain injury caused by avariety of neurological insults and may eventually play an importantrole in emergency brain resuscitation. Experimental evidence hasdemonstrated that cerebral cooling improves outcome after globalischemia, focal ischemia, or traumatic brain injury. For this reason,hypothermia may be induced in order to reduce the effect of certainbodily injuries to the brain as well as other organs.

Cerebral hypothermia has traditionally been accomplished through wholebody cooling to create a condition of total body hypothermia in therange of 20° C. to 30° C. However, the use of total body hypothermiarisks certain deleterious systematic vascular effects. For example,total body hypothermia may cause severe derangement of thecardiovascular system, including low cardiac output, elevated systematicresistance, and ventricular fibrillation. Other side effects includerenal failure, disseminated intravascular coagulation, and electrolytedisturbances. In addition to the undesirable side effects, total bodyhypothermia is difficult to administer.

Catheters have been developed which are inserted into the bloodstream ofthe patient in order to induce total body hypothermia. For example, U.S.Pat. No. 3,425,419 to Dato describes a method and apparatus of loweringand raising the temperature of the human body. The Dato invention isdirected towards a method of inducing moderate hypothermia in a patientusing a metallic catheter. The metallic catheter has an inner passagewaythrough which a fluid, such as water, can be circulated. The catheter isinserted through the femoral vein and then through the inferior venacava as far as the right atrium and the superior vena cava. The Datocatheter has an elongated cylindrical shape and is constructed fromstainless steel. By way of example, Dato suggests the use of a catheterapproximately 70 cm in length and approximately 6 mm in diameter.However, use of the Dato invention implicates the negative effects oftotal body hypothermia described above.

Due to the problems associated with total body hypothermia, attemptshave been made to provide more selective cooling. For example, coolinghelmets or head gear have been used in an attempt to cool only the headrather than the patient's entire body. However, such methods rely onconductive heat transfer through the skull and into the brain. Onedrawback of using conductive heat transfer is that the process ofreducing the temperature of the brain is prolonged. Also, it isdifficult to precisely control the temperature of the brain when usingconduction due to the temperature gradient that must be establishedexternally in order to sufficiently lower the internal temperature. Inaddition, when using conduction to cool the brain, the face of thepatient is also subjected to severe hypothermia, increasing discomfortand the likelihood of negative side effects. It is known that profoundcooling of the face can cause similar cardiovascular side effects astotal body cooling. From a practical standpoint, such devices arecumbersome and may make continued treatment of the patient difficult orimpossible.

Selected organ hypothermia has been accomplished using extracorporealperfusion, as detailed by Arthur E. Schwartz, M. D. et al., in IsolatedCerebral Hypothermia by Single Carotid Artery Perfusion ofExtracorporeally Cooled Blood in Baboons, which appeared in Vol. 39, No.3, NEUROSURGERY 577 (September, 1996). In this study, blood wascontinually withdrawn from baboons through the femoral artery. The bloodwas cooled by a water bath and then infused through a common carotidartery with its external branches occluded. Using this method, normalheart rhythm, systemic arterial blood pressure and arterial blood gasvalues were maintained during the hypothermia. This study showed thatthe brain could be selectively cooled to temperatures of 20° C. withoutreducing the temperature of the entire body. However, externalcirculation of blood is not a practical approach for treating humansbecause the risk of infection, need for anticoagulation, and risk ofbleeding is too great. Further, this method requires cannulation of twovessels making it more cumbersome to perform particularly in emergencysettings. Even more, percutaneous cannulation of the carotid artery isdifficult and potentially fatal due to the associated arterial walltrauma. Finally, this method would be ineffective to cool other organs,such as the kidneys, because the feeding arteries cannot be directlycannulated percutaneously.

Selective organ hypothermia has also been attempted by perfusion of acold solution such as saline or perflourocarbons. This process iscommonly used to protect the heart during heart surgery and is referredto as cardioplegia. Perfusion of a cold solution has a number ofdrawbacks, including a limited time of administration due to excessivevolume accumulation, cost, and inconvenience of maintaining theperfusate and lack of effectiveness due to the temperature dilution fromthe blood. Temperature dilution by the blood is a particular problem inhigh blood flow organs such as the brain.

Therefore, a practical method and apparatus which modifies and controlsthe temperature of a selected organ satisfies a long-felt need.

SUMMARY OF THE INVENTION

A heat transfer device comprises first and second elongated, articulatedsegments, each the segment having a turbulence-inducing exteriorsurface. A flexible joint can connect the first and second elongated,articulated segments. An inner coaxial lumen may be disposed within thefirst and second elongated, articulated segments and is capable oftransporting a pressurized working fluid to a distal end of the firstelongated, articulated segment. In addition, the first and secondelongated, articulated segments may have a turbulence-inducing interiorsurface for inducing turbulence within the pressurized working fluid.The turbulence-inducing exterior surface may be adapted to induceturbulence within a free stream of blood flow when placed within anartery. The turbulence-inducing exterior surface may be adapted toinduce a turbulence intensity with in a free stream blood flow which isgreater than 0.05. In one embodiment, the flexible joint comprisesbellows sections which allow for the axial compression of the heattransfer device.

In one embodiment, the turbulence-inducing exterior surfaces compriseinvaginations configured to have a depth which is greater than athickness of a boundary layer of blood which develops within an arterialblood flow. The first elongated, articulated segment may comprisecounter-clockwise invaginations while the second elongated, articulatedsegment comprises clockwise invaginations. The first and secondelongated, articulated segments may be formed from highly conductivematerial.

In another embodiment, the turbulence-inducing exterior surface isadapted to induce turbulence throughout the duration of each pulse of apulsatile blood flow when placed within an artery. In still anotherembodiment, the turbulence-inducing exterior surface is adapted toinduce turbulence during at least 20% of the period of each cardiaccycle when placed within an artery.

The heat transfer device may also have a coaxial supply catheter with aninner catheter lumen coupled to the inner coaxial lumen within the firstand second elongated, articulated segments. A working fluid supplyconfigured to dispense the pressurized working fluid may be coupled tothe inner catheter lumen. The working fluid supply may be configured toproduce the pressurized working fluid at a temperature of about 0° C.and at a pressure below 5 atmospheres of pressure.

In yet another alternative embodiment, the heat transfer device may alsohave a third elongated, articulated segment having a turbulence-inducingexterior surface and a second flexible joint connecting the second andthird elongated, articulated segments. In one embodiment, the first andthird elongated, articulated segments may comprise clockwiseinvaginations if the second elongated, articulated segment comprisescounter-clockwise invaginations. Alternatively, the first and thirdelongated, articulated segments may comprise counter-clockwiseinvaginations if the second elongated, articulated segment comprisesclockwise invaginations.

The turbulence-inducing exterior surface may optionally include asurface coating or treatment to inhibit clot formation. One variation ofthe heat transfer device comprises a stent coupled to a distal end ofthe first elongated, articulated segment.

The present invention also envisions a method of treating the brainwhich comprises the steps of inserting a flexible, conductive heattransfer element into the carotid artery from a distal location, andcirculating a working fluid through the flexible, conductive heattransfer element in order to selectively modify the temperature of thebrain without significantly modifying the temperature of the entirebody. The flexible, conductive heat transfer element preferably absorbsmore than 25, 50 or 75 Watts of heat.

The method may also comprise the step of inducing turbulence within thefree stream blood flow within the carotid artery. In one embodiment, themethod includes the step of inducing blood turbulence with a turbulenceintensity greater than 0.05 within the carotid artery. In anotherembodiment, the method includes the step of inducing blood turbulencethroughout the duration of the period of the cardiac cycle within thecarotid artery. In yet another embodiment, the method comprises the stepof inducing blood turbulence throughout the period of the cardiaccyclewithin the carotid artery or during greater than 20% of the periodof the cardiac cycle within the carotid artery. The step of circulatingmay comprise the step of inducing turbulent flow of the working fluidthrough the flexible, conductive heat transfer element. The pressure ofthe working fluid may be maintained below 5 atmospheres of pressure.

The present invention also envisions a method for selectively cooling anorgan in the body of a patient which comprises the steps of introducinga catheter into a blood vessel supplying the organ, the catheter havinga diameter of 4 mm or less, inducing free stream turbulence in bloodflowing over the catheter, and cooling the catheter to remove heat fromthe blood to cool the organ without substantially cooling the entirebody. In one embodiment, the cooling step removes at least about 75Watts of heat from the blood. In another embodiment, the cooling stepremoves at least about 100 Watts of heat from the blood. The organ beingcooled may be the human brain.

The step of inducing free stream turbulence may induce a turbulenceintensity greater than 0.05 within the blood vessel. The step ofinducing free stream turbulence may induce turbulence throughout theduration of each pulse of blood flow. The step of inducing free streamturbulence may induce turbulence for at least 20% of the duration ofeach pulse of blood flow.

In one embodiment, the catheter has a flexible metal tip and the coolingstep occurs at the tip. The tip may have turbulence-inducing segmentsseparated by bellows sections. The turbulence-inducing segments maycomprise invaginations which are configured to have a depth which isgreater than a thickness of a boundary layer of blood which developswithin the blood vessel. In another embodiment, the catheter has a tipat which the cooling step occurs and the tip has turbulence inducingsections that alternately spiral bias blood flow in clockwise andcounterclockwise directions.

The cooing step may comprise the step of circulating a working fluid inthrough an inner lumen in the catheter and out through an outer, coaxiallumen. In one embodiment, the working fluid remains a liquid. Theworking fluid may be aqueous.

The present invention also envisions a cooling catheter comprising acatheter shaft having first and second lumens therein. The coolingcatheter also comprises a cooling tip adapted to transfer heat to orfrom a working fluid circulated in through the first lumen and outthrough the second lumen, and turbulence-inducing structures on thecooling tip capable of inducing free stream turbulence when the tip isinserted into a blood vessel. The turbulence-inducing structures mayinduce a turbulence intensity of at least about 0.05. The cooling tipmay be adapted to induce turbulence within the working fluid. Thecatheter is capable of removing least about 25 Watts of heat from anorgan when inserted into a vessel supplying that organ, while coolingthe tip with a working fluid that remains a liquid in the catheter.Alternatively, the catheter is capable of removing at least about 50 or75 Watts of heat from an organ when inserted into a vessel supplyingthat organ, while cooling the tip with an aqueous working fluid. In oneembodiment, in use, the tip has a diameter of 4 mm or less. Optionally,the turbulence-inducing structures comprise invaginations which have adepth sufficient to disrupt the free stream blood flow in the bloodvessel. Alternatively, the turbulence-inducing structures may comprisestaggered protrusions which have a height sufficient to disrupt the freestream flow of blood within the blood vessel.

In another embodiment, a cooling catheter may comprise a catheter shafthaving first and second lumens therein, a cooling tip adapted totransfer heat to or from a working fluid circulated in through the firstlumen and out through the second lumen, and turbulence-inducingstructures on the cooling tip capable of inducing turbulence when thetip is inserted into a blood vessel. Alternatively, a cooling cathetermay comprise a catheter shaft having first and second lumens therein, acooling tip adapted to transfer heat to or from a working fluidcirculated in through the first lumen and out through the second lumen,and structures on the cooling tip capable of inducing free streamturbulence when the tip is inserted into a blood vessel. In anotherembodiment, a cooling catheter may comprise a catheter shaft havingfirst and second lumens therein, a cooling tip adapted to transfer heatto or from a working fluid circulated in through the first lumen and outthrough the second lumen, and turbulence-inducing structures on thecooling tip capable of inducing turbulence with an intensity greaterthan about 0.05 when the tip is inserted into a blood vessel.

BRIEF DESCRIPTION OF THE DRAWINGS

The features, objects, and advantages of the invention will become moreapparent from the detailed description set forth below when taken inconjunction with the drawings in which like reference charactersidentify corresponding throughout and wherein:

FIG. 1 is a graph illustrating the velocity of steady state turbulentflow as a function of time.

FIG. 2A is a graph showing the velocity of the blood flow within anartery as a function of time.

FIG. 2B is a graph of illustrating the velocity of steady stateturbulent flow under pulsatile conditions as a function of time similarto those seen in arterial blood flow.

FIG. 2C is a perspective view of a turbulence inducing heat transferelement within an artery which indicates where the turbulent flow ismeasured within the artery in relation to the heat transfer element.

FIG. 3A is a velocity profile diagram showing a typical steady statePoiseuillean flow driven by constant pressure gradient.

FIG. 3B is a velocity profile diagram showing blood flow velocity withinan artery averaged over the cardiac pulse.

FIG. 3C is a velocity profile diagram showing blood flow velocity withinan artery averaged over the cardiac pulse upon insertion of a smoothheat transfer element within a blood vessel.

FIG. 4 is a perspective view of one embodiment of a heat transferelement according to the invention.

FIG. 5 is longitudinal sectional view of the heat transfer element ofFIG. 4.

FIG. 6 is a transverse cross-sectional conceptural view of the heattransfer element of FIG. 4.

FIG. 7 is a cut-away perspective view of the heat transfer element ofFIG. 4 in use within a blood vessel.

FIG. 8 is a cut-away perspective view of an alternative embodiment of aheat transfer element.

FIG. 9 is a transverse cross-sectional view of the heat transfer elementof FIG. 8.

FIG. 10 is a schematic representation of the invention being used tocool the brain of a patient

DETAILED DESCRIPTION OF THE INVENTION

In order to intravascularly regulate the temperature of a selectedorgan, a heat transfer element may be placed in the feeding artery ofthe organ to absorb or deliver the heat from or to the blood flowinginto the organ. The transfer of heat may cause either a cooling or aheating of the selected organ. The heat transfer element must be smallenough to fit within the feeding artery while still allowing asufficient blood flow to reach the organ in order to avoid ischemicorgan damage. A heat transfer element which selectively cools an organshould be capable of providing the necessary heat transfer rate toproduce the desired cooling or heating effect within the organ. Byplacing the heat transfer element within the feeding artery of an organ,the temperature of an organ can be controlled without significantlyeffecting the remaining parts of the body. These points can beillustrated by using brain cooling as an example.

The common carotid artery supplies blood to the head and brain. Theinternal carotid artery branches off of the common carotid to directlysupply blood to the brain. To selectively cool the brain, the heattransfer element is placed into the common carotid artery, the internalcarotid artery, or both. The internal diameter of the common carotidartery ranges from 6 to 8 mm and the length ranges from 80 to 120 mm.Thus, the heat transfer element residing in one of these arteries cannotbe much larger than 4 mm in diameter in order to avoid occluding thevessel.

It is important that the heat transfer element be flexible in order tobe placed within the small feeding artery of an organ. Feeding arteries,like the carotid artery, branch off the aorta at various levels.Subsidiary arteries continue to branch off the initial branches. Forexample, the internal carotid artery is a small diameter artery thatbranches off of a common carotid artery near the angle of the jaw.Because the heat transfer element is typically inserted into aperipheral artery, such as the femoral artery, and accesses the feedingartery by initially passing though a series of one or more of thesebranch, the flexibility of the heat transfer element is an importantcharacteristic of the heat transfer element. Further, the heat transferelement is ideally constructed from a high thermally conductive materialsuch as metal in order to facilitate heat transfer. The use of a highthermally conductive material increases the heat transfer rate for agiven temperature differential between the coolant within the heattransfer element and the blood. This facilitates the use of a highertemperature coolant within the heat transfer element, allowing safercoolants such as water to be used. High thermally conductive materials,such as metals, tend to be rigid. The design of the heat transferelement should facilitate flexibility in an inherently inflexiblematerial.

In order to obtain the benefits of hypothermia described above, it isdesirable to reduce the temperature of the blood flowing to the brain tobetween 30° C. and 32° C. Given that a typical brain has a blood flowrate through each carotid artery (right and left) of approximately250-375 cubic centimeters per minute (cc/min), the heat transfer elementshould absorb 75-175 Watts of heat when placed in one of the carotidarteries in order to induce the desired cooling effect. It should benoted that smaller organs may have less blood flow in the supply arteryand may require less heat transfer such as 25 Watts.

When a heat transfer element is inserted coaxially into an artery, theprimary mechanism of heat transfer between the surface of the heattransfer element and the blood is forced convection. Convection reliesupon the movement of fluid to transfer heat. Forced convection resultswhen an external force causes motion within the fluid. In the case ofarterial flow, the beating heart causes the motion of the blood aroundthe heat transfer element.

Equation 1 is Newton's law of convection which provides an estimate ofthe rate of heat transfer between the blood and the heat transferelement.

    Q=h.sub.c SΔT                                        Equation 1

where Q is the heat transfer rate in Watts;

S is the area of the heat transfer element in direct contact with thefluid in meters squared (m²);

ΔT is the temperature differential between the surface temperature,T_(s), of the heat transfer element and the free stream bloodtemperature, T_(b), in degrees Kelvin (K); and

h_(c) is the average convection heat transfer coefficient over the heattransfer area in units of Watts per meter squared degrees Kelvin (W/m²K), and is some times called the surface coefficient of heat transfer orthe convection heat transfer coefficient.

The magnitude of the heat transfer rate, Q, can be increased throughmanipulation of the three parameters which determine its value: h_(c) ,S, and ΔT. Practical constraints limit the value of these parameters.

As noted above, the receiving artery into which the heat transferelement is placed has a limited diameter and length. Thus, the crosssectional area of the heat transfer element should be limited so as toavoid significant obstruction of the blood flow through the artery. Thelength of the heat transfer element should also be limited so that theheat transfer element is small enough to fit into the receiving artery.For placement within the internal and common carotid artery, the crosssectional diameter of the heat transfer element is limited to about 4mm, and its length is limited to approximately 10 cm. Consequently, thevalue of the surface area, S, is limited by the physical constraintsimposed by the size of the artery into which the device is placed.Surface features, such as fins, can be used to increase the surface areaof the heat transfer element, however, these features alone cannotprovide enough surface area enhancement to meet the required heattransfer rate to effectively cool the brain.

For the case where the heat transfer element is used to inducehypothermia, the value of ΔT=T_(b) -T_(s) can be increased by decreasingthe surface temperature, T_(s), of the heat transfer element. However,the allowable surface temperature is limited by the characteristics ofblood. Blood freezes at approximately 0° C. When the blood approachesfreezing, ice emboli may form in the blood which may lodge downstream,causing serious ischemic injury. Furthermore, reducing the temperatureof the blood also increases its viscosity which also results in a smalldecrease in the value of the convection heat transfer coefficient, h_(c). In addition, increased viscosity of the blood may result in anincrease in the pressure drop within the artery, thus, compromising theflow of blood to the brain. Given the above constraints, it isadvantageous to limit the surface temperature of the heat transferelement to approximately 5° C., thus, resulting in a maximum temperaturedifferential between the blood stream and the heat transfer element ofapproximately 32° C.

The mechanisms by which the value of convection heat transfercoefficient, h_(c) , may be increased are complex. However, it is wellknown that the convection heat transfer coefficient, h_(c) , increaseswith the level of turbulent kinetic energy in the fluid flow. Thus it isadvantageous to have turbulent blood flow in contact with the heattransfer element.

Arterial blood flow is completely bound by a solid surface (i.e. thearterial wall) and is called an internal flow. Internal flows may becharacterized as laminar or turbulent. In the laminar regime, flowstructure is characterized by smooth motion in laminae or layers.Laminar flow has no turbulent kinetic energy. Flow structure in theturbulent regime is characterized by random, three-dimensional motionsof fluid particles superimposed on the mean motion. FIG. 1 is a graphillustrating steady state turbulent flow. The vertical axis is thevelocity of the flow. The horizontal axis represents time. The averagevelocity of the turbulent flow is shown by a line 100. The actualinstantaneous velocity of the flow is shown by a curve 102.

The level of turbulence can be characterized by the turbulenceintensity. Turbulence intensity, , is defined as the square root of thefluctuating velocity divided by the mean velocity as given in Equation2. ##EQU1## where u' is the magnitude of the time-varying portion of thevelocity; and u is the average velocity.

For example, referring again to FIG. 1, the velocity of the time-varyingportion of the velocity, u', is represented by the size of the peaks andvalleys on the curve 102. The average velocity, u, is represented by theline 100.

The most basic fluid mechanic equations predict the behavior of internalpipe flows under a uniform and constant pressure. Under these conditionsthe flow is Poiseuillean. FIG. 3A is a velocity profile diagram showinga typical steady state Poiseuillean flow driven by constant pressure.The velocity of the fluid across the pipe is shown in FIG. 3A by theparabolic curve and corresponding velocity vectors. The velocity of thefluid in contact with the wall of the pipe is zero. The boundary layeris the region of the flow in contact with the pipe surface in whichviscous stresses are dominant. In the steady state Poiseuillean flow,the boundary layer develops until it reaches the pipe center line. Forexample, the boundary layer thickness, δ, in FIG. 3A is one half of thediameter of the pipe, D_(a). FIG. 3A is introduced for comparisonpurposes to show the difference between standard Poiseuillean flow andthe flow which develops within an artery.

Under conditions of Poiseuillean flow, the Reynolds number, Re, can beused to characterize the level of turbulent kinetic energy. The Reynoldsnumber, Re, is the ratio of inertial forces to viscous forces and isgiven by Equation 3: ##EQU2## where: D_(a) is the diameter of the arteryin meters (m); U is the flow velocity of the blood in meters/second(m/s);

ρ is the density of the blood in kilograms per meters cubed (kg/m³); and

μ is the absolute viscosity of the blood in meters squared per second(m³ /s).

For Poiseuillean flows, Reynolds numbers, Re, must be greater than about2300 to cause a laminar to turbulent transition. Further, underconditions of high Reynolds numbers (>2000), the boundary layer isreceptive to "tripping". Tripping is a process by which a smallperturbation in the boundary layer amplifies to turbulent conditions.The receptivity of a boundary layer to "tripping" is proportional to theReynolds, Re, number and is nearly zero for Reynolds, Re, numbers lessthan 2000.

However, the blood flow in the arteries is induced by the beating heartand is pulsatile, complicating the turbulent fluid mechanics analysisabove. FIG. 2A is a graph showing the velocity of the blood flow withinan artery as a function of time. The beating heart provides pulsatileflow with an approximate period of 0.5 to 1 second. This is known as theperiod of the cardiac cycle. The horizontal axis in FIG. 2A representstime in seconds and the vertical axis represents the average velocity ofblood in centimeters per second (cm/s). Although very high velocitiesare reached at the peak of the pulse, the high velocity occurs for onlya small portion of the cycle. In fact, the velocity of the blood reacheszero in the carotid artery at the end of a pulse and temporarilyreverses.

Because of the relatively short duration of the cardiac pulse, the bloodflow in the arteries does not develop into classic Poiseuillean flow.FIG. 3B is a velocity profile diagram showing blood flow velocity withinan artery averaged over the cardiac pulse. Notice that the majority ofthe flow within the artery has the same velocity. The character of thepulsed flow in an artery of diameter, D_(a), is determined by the valueof a dimensionless parameter called the Womersley number. The Womersleynumber expresses the ratio between oscillatory inertia forces andviscous shear forces and is also proportional to the interior diameterof the artery and inversely proportional to the thickness of theboundary layer as given in Equation 4. ##EQU3## where ω is the frequencyof the pulsating force in cycles per second (l/s);

D_(a) is the diameter of the artery in meters (m);

ρ is the density of the blood in kilograms per meters cubed (kg/m³);

μ is the absolute viscosity of the blood in meters squared per second(m³ /s); and

δ is the boundary layer thickness in meters (m).

The Womersley number is relatively high (N_(w) =15-20) in the aorta andin the common carotid artery (N_(w) =6-10). The relatively highWomersley numbers results in the relatively blunt velocity profile incontrast to the parabolic profile of the steady state viscousPoiseuillean flow. In other words, the arterial flow is predominatelycomposed of an inviscid "free stream" and a very thin viscous boundarylayer adjacent to the artery wall. "Free stream" refers to the flowwhich is not affected by the presence of the solid boundaries and inwhich the average velocity remains fairly constant as a function ofposition within the artery. The motion in the boundary layer is mainlythe result of the balance between inertia and viscous forces, while inthe free stream, the motion is the result of the balance between inertiaand pressure forces. In FIG. 3B, notice that the boundary layer wherethe flow velocity decays from the free stream value to zero is verythin, typically 1/6 to 1/20 of the diameter of the artery, as opposed toone half of the diameter of the artery in the Poiseuillean flowcondition.

As noted above, if the flow in the artery were steady rather thanpulsatile, the transition from laminar to turbulent flow would occurwhen the value of the Reynolds number, Re, exceeds about 2,300. However,in the pulsatile arterial flow, the value of the Reynolds number, Re,varies during the cardiac cycle, just as the flow velocity, U, varies.In pulsatile flows, due to the enhanced stability of associated with theacceleration of the free stream flow, the critical value of the Reynoldsnumber, Re, at which the unstable modes of motion grow into turbulenceis found to be much higher, perhaps as high as 9,000. The critical valueof the Reynolds number, Re, at which laminar flow transitions intoturbulent flow increases with increasing values of the Womersley number.Consequently, the blood flow in the arteries of interest remains laminarover more than 80% of the cardiac cycle. Referring again to FIG. 2A, theblood flow is turbulent from approximately time t₁ until time t₂ duringa small portion of the descending systolic flow which is less than 20%of the period of the cardiac cycle. It can be seen from FIG. 2A thatturbulence does occur for a short period in the cardiac cycle. If a heattransfer element is placed co axially inside the artery, the heattransfer rate will be facilitated during this short interval. However,to transfer the necessary heat to cool the brain, turbulent kineticenergy may be produced and may be sustained throughout the entire periodof the cardiac cycle. The existence of a free stream becomes significantwhen designing a heat transfer element to transfer heat from a selectedorgan. Because of the acceleration of the free stream and its inherentstability, simple surface features on the heat transfer element, such asfins or wires, will not produce a laminar to turbulent transition.

A thin boundary layer is noted to form during thecardiac cycle. Thisboundary layer will form over the surface of a smooth heat transferelement. FIG. 3C is a velocity profile diagram showing blood flowvelocity within an artery averaged over the cardiac pulse upon insertionof a smooth heat transfer element 18 within a blood vessel. In FIG. 3C,the diameter of the heat transfer element 18, D, is about one half ofthe diameter of the artery, D_(a). Notice that boundary layers developadjacent to the heat transfer element 18 as well as the walls of theartery. Each of these boundary layers has approximately the samethickness, δ, as the boundary layer which would have developed at thewall of the artery in the absence of the heat transfer element 18. Thefree stream flow region is developed in an annular ring around the heattransfer element 18.

One way to increase the heat transfer rate is to create a turbulentboundary layer on the heat transfer element surface. However, "tripping"mechanisms, such as placing a wire or fin on the smooth surface of theheat transfer element shown, will not work. This is due to the lowReynolds numbers in arterial flow which are less than 250 for more thanhalf the cycle (i.e. the receptivity to tripping is extremely low).

The arterial flow is predominantly free stream and inherently stablesuch that very high Reynolds number must be found before a laminar toturbulent transition takes place. Although a thin boundary layer forms,simple fins or coiled wires on a heat transfer element will not producesustained turbulent kinetic energy in the boundary layer and produce thenecessary heat transfer rate. Therefore, to induce turbulent kineticenergy and increase the heat transfer rate sufficiently to cool thebrain by a catheter placed in the common carotid, stirring typemechanisms, which abruptly change the direction of velocity vectors, maybe utilized. This can create high levels of turbulence intensity in thefree stream thereby increasing the heat transfer rate.

This turbulence intensity should ideally be sustained for a significantportion of the cardiac cycle. The turbulent kinetic energy shouldideally be created throughout the free stream and not just in theboundary layer. FIG. 2B is a graph illustrating the velocity of steadystate turbulent flow under pulsatile conditions as a function of timesimilar to those seen in an arterial blood flow. FIG. 2C is aperspective view of a turbulence inducing heat transfer element withinan artery which indicates point 114 where the turbulent flow is measuredwithin the artery in relationship to the heat transfer element. Notethat turbulent velocity fluctuations are seen throughout the cycle asopposed to the short interval of fluctuations seen in FIG. 2A betweentime t₁ until time t₂. These velocity fluctuations are found within thefree stream. The turbulence intensity is at least 0.05. In other words,the instantaneous velocity fluctuations deviate from the mean velocityby at least 5%. Although ideally turbulence is created throughout theentire period of the cardiac cycle, the benefits of turbulence areobtained if the turbulence is sustained for 75%, 50% or even as low as30% or 20% of the cardiac cycle.

To create the desired level of turbulence intensity in the blood freestream during the whole cardiac cycle, in one embodiment, the inventionuses a modular design which produces high level of turbulence in thefree stream by periodically forcing abrupt changes in the direction ofthe blood flow. The abrupt changes in flow direction are achievedthrough the use of a series of two or more segments each comprised ofinvaginations or protrusions. To affect the free stream, the size of theinvaginations or protrusions is larger than the thickness of theboundary layer which would develop if a smooth heat transfer elementwould be introduced into the blood stream.

The use of periodic abrupt changes in the direction of the blood flow inorder to induce strong free stream turbulence may be illustrated withreference to a common clothes washing machine. The rotor of a washingmachine spins initially in one direction causing laminar flow. When therotor abruptly reverses direction, significant turbulent kinetic energyis created within the entire wash basin as the changing currents causerandom turbulent motion within the clothes-water slurry.

FIG. 4 is a perspective view of one embodiment of a heat transferelement according to the present invention. A heat transfer element 14is comprised of a series of articulating segments or modules. As seen inFIG. 4, a first articulating segment 20 is located at the distal end ofthe heat transfer element 14. A turbulence-inducing exterior surface 28of the segment 20 is formed from one or more invaginations 26. Withinthe segment 20, the spiraling invaginations 26 rotate in a clockwisedirection as they proceed towards the distal end of the heat transferelement 14. The segment 20 is coupled to a second segment 24 via abellows section 22 to provide flexibility. The second segment 24 isformed from one or more spiraling invaginations 30. The spiralinginvaginations 30 rotate in a counter-clockwise direction as they proceedtowards the distal end of the heat transfer element 14. The segment 24is followed by a third segment 20 having the clockwise invaginations 26.Thus, successive segments of the heat transfer element 14 alternatebetween having clockwise and counterclockwise invaginations. Inaddition, the rounded invaginations also allow the heat transfer elementto maintain a relatively atraumatic profile in comparison to the use ofribs or fins, thereby minimizing the possibility of damage to the vesselwall. A heat transfer element may be comprised of 1, 2, 3 or moresegments.

The bellows sections 22 are formed from seamless and nonporousmaterials, such as metal, and therefore are impermeable to gas which canbe particularly important depending on the type of working fluid whichis cycled through the heat transfer element 14. The structure of thebellows sections 22 allows them to bend, extend and compress whichincreases the flexibility of the heat transfer element so that it ismore readily able to navigate through tiny blood vessels. The bellowssections 22 also provide for axial compression of the heat transferelement 14 which can limit the trauma when the distal end of the heattransfer element 14 abuts a blood vessel wall. The bellows sections 22are also able to tolerate cryogenic temperatures without a loss ofperformance.

The exterior surface 28 of the heat transfer element 14 can be made frommetal, and may comprise very high thermally conductive material such asnickel, thereby, facilitating heat transfer. Alternatively, other metalssuch as stainless steel, titanium, aluminum, silver, copper and thelike, can be used, with or without an appropriate coating or treatmentto enhance biocompatibility or inhibit clot formation. Suitablebiocompatible coatings include, e.g., gold, platinum or polymerparalyene. The heat transfer element 14 may be manufactured by plating athin layer of metal on a mandrel that has the appropriate pattern. Inthis way, the heat transfer element 14 may be manufactured inexpensivelyin large quantities which is an important feature in a disposablemedical device.

Because the heat transfer element 14 may dwell within the blood vesselfor extended periods of time such as 24-48 hours or even longer, it maybe desirable to treat the surface 28 of the heat transfer element 14 toavoid clot formation. In particular, one may wish to treat the bellowssections 22 because stagnation of the blood flow may occur in theconvolutions, thus, allowing clots to form and cling to the surface toform a thrombus. One means by which to prevent thrombus formation is tobind an antithrombogenic agent to the surface of the heat transferelement 14. For example, heparin is known to inhibit clot formation andis also known to be useful as a biocoating. Alternatively, the surface28 of the heat transfer element 14 may be bombarded with ions such asnitrogen. Bombardment with nitrogen can harden and smooth the surface 28and, thus, prevent adherence of clotting factors to the surface 28.

FIG. 5 is longitudinal sectional view of the heat transfer element ofthe invention, taken along line 5--5 in FIG. 4. Once the heat transferelement 14 is in place, a working fluid such as saline or other aqueoussolution may be circulated through the heat transfer element 14. Fluidflows up a supply catheter into an insulated inner coaxial lumen 40. Atthe distal end of the heat transfer element 14, the working fluid exitsthe inner coaxial lumen 40 and enters an outer lumen 46. As the workingfluid flows through the outer lumen 46, heat is transferred from theworking fluid to the exterior surface 28 of the heat transfer element14. Because the heat transfer element 14 is constructed from highlyconductive material, the temperature of the external surface 28 mayreach very close to the temperature of the working fluid. In order toavoid the loss of thermal energy from the working fluid within the innercoaxial lumen 40, an insulating coaxial layer 42 may be provided withinthe heat transfer element 14. The insulating coaxial layer 42 iscomprised of a non-thermally conductive material. For example,insulation may be achieved by creating longitudinal air channels in thewalls of the insulating coaxial layer 42. Alternatively, the insulatingcoaxial layer 42 may be constructed of a non-thermally conductivematerial like polytetrafluoroethylene or other polymer.

It is important to note that the same mechanisms that govern the heattransfer rate between the external surface 28 of the heat transferelement and the blood also govern the heat transfer rate between theworking fluid and the inside surface of the heat transfer element. Theheat transfer characteristics of the internal structure is particularlyimportant when using water, saline or other fluid which remains a liquidas the coolant. Other coolants such as freon, undergo nucleated boilingand create turbulence through a different mechanism. Saline is a safecoolant because it is non toxic and leakage of saline does not result ina gas embolism which may occur with the use of boiling refrigerants. Byalso enhancing turbulence in the coolant, the coolant can be deliveredto the heat transfer element at a warmer temperature and still achievethe necessary heat transfer rate. This has a number of beneficialimplications in the need for insulation along the catheter shaft length.Due to the decreased need for insulation, the catheter shaft diametercan be made smaller. The enhanced heat transfer characteristics of theinternal structure also allow the working fluid to be delivered to theheat transfer element at lower flow rates and lower pressures. Highpressures may make the heat transfer element stiff and cause it to pushagainst the wall of the vessel, thereby shielding part of the heattransfer unit from the blood. Because of the increased heat transfercharacteristics, the pressure of the working fluid may be as low as 5atmospheres, 3 atmospheres, 2 atmospheres or even less than 1atmosphere.

FIG. 6 is a transverse cross-sectional conceptural view of the heattransfer element of the invention, taken along the line 6--6 in FIG. 4.In FIG. 6, the coaxial construction of the heat transfer element 14 isclearly shown. The inner coaxial lumen 40 is defined by the insulatingcoaxial layer 42. The outer lumen 44 is defined by the exterior surfaceof the insulating coaxial layer 42 and the interior surface of the heattransfer element 14. In addition, the spiraling invaginations 26 and theexternal surface 28 may be seen in FIG. 6. As noted above, in thepreferred embodiment, the depth of the invaginations, d_(i), is greaterthan the boundary layer thickness, δ, which would have developed if asmooth heat transfer element were introduced. For example, in a heattransfer element with a 4 mm outer diameter, the depth of theinvaginations, d_(i), may be approximately equal to 1 mm if designed foruse in the carotid artery. Although FIG. 6 shows five invaginations, thenumber of invaginations may vary. Thus, heat transfer elements with 1,2, 3, 4, 5, 6, 7, 8 or more invaginations are specifically contemplated.

FIG. 7 is a cut-away perspective view of the heat transfer element 14 inuse within a blood vessel. Beginning from the proximal end of the heattransfer element (not shown in FIG. 7), as the blood moves forwardduring the systolic pulse, the first invaginated segment induces arotational inertia to the blood. As the blood reaches the secondsegment, the rotational direction of the inertia is reversed, causingturbulence within the blood. The sudden change in flow directionactively reorients and randomizes the velocity vectors, thus, ensuringturbulence throughout the bloodstream. During turbulent flow, thevelocity vectors of the blood become more random and, in some cases,become perpendicular to the axis of the artery. In addition, as thevelocity of the blood within the artery decreases and reverses directionduring the cardiac cycle, additional turbulence is induced and turbulentmotion is sustained throughout the duration of each pulse through thesame mechanisms described above.

Thus, a large portion of the volume of warm blood in the vessel isactively brought in contact with the heat transfer element, where it canbe cooled by direct contact, rather than being cooled largely byconduction through adjacent laminar layers of blood. As noted above, thedepth of the invaginations is greater than the depth of the boundarylayer which would develop if a smooth heat transfer element would beintroduced into the blood stream. In this way, the free streamturbulence is induced. In introduced into the blood stream. In this way,the free stream turbulence is induced. In the preferred embodiment, inorder to create the desired level of turbulence in the entire bloodstream during the whole cardiac cycle, the heat transfer element createsa turbulence intensity greater than 0.05. The turbulence intensity maybe greater than 0.055, 0.06, 0.07 or up to 0.10 or 0.20 or greater. Ifthe heat transfer element according to the invention were placed in apipe approximately the same size as an artery carrying a fluid having asimilar velocity, density and viscosity of blood and having a constant(rather than pulsatile) flow, Reynolds numbers of greater than 1,900,2,000, 2,100, 2,200 or even as much as 2,300, 2,400 or 2,600 or greaterwould be developed. Further, the design shown in FIGS. 4, 5, 6 and 7provides a similar mixing action for the working fluid inside the heattransfer element.

The heat transfer element 14 has been designed to address all of thedesign criteria discussed above. First, the heat transfer element 14 isflexible and is made of highly conductive material. The flexibility isprovided by a segmental distribution of bellows sections which providesan articulating mechanism. Bellows have a known convoluted design whichprovides flexibility. Second, the surface area has been increasedthrough spiral invaginations or grooves. The invaginations also allowthe heat transfer element to maintain a relatively atraumatic profile incomparison to the use of ribs or fins, thereby minimizing thepossibility of damage to the vessel wall. Third, the heat transferelement 14 has been designed to promote turbulent kinetic energy bothinternally and externally. The modular or segmental design allows thedirection of the invaginations to be reversed with each segment. Thealternating invaginations create an alternating flow that results inmixing the blood in a manner analogous to the mixing action created bythe rotor of a washing machine that switches directions back and forth.This mixing action is intended to promote the high level turbulentkinetic energy to enhance the heat transfer rate. The invaginated designalso causes the beneficial mixing, or turbulent kinetic energy, of theworking fluid flowing internally.

FIG. 8 is a cut-away perspective view of an alternative embodiment of aheat transfer element 50. An external surface 52 of the heat transferelement 50 is covered with a series of staggered protrusions 54. Thestaggered nature of the protrusions 54 is readily seen with reference toFIG. 9 which is a transverse cross-sectional view taken of the staggeredprotrusions 54 is greater than the thickness of the boundary layer whichwould develop if a smooth heat transfer element had been introduced intothe blood stream. As the blood flows along the external surface 52, itcollides with one of the staggered protrusions 54 and a turbulent flowis created. As the blood divides and swirls along side of the firststaggered protrusion 54, it collides with another staggered protrusion54 within its path preventing the re-lamination of the flow and creatingyet more turbulence. In this way, the velocity vectors are randomizedand free stream turbulence is created. As is the case with the preferredembodiment, this geometry also induces a turbulent effect on theinternal coolant flow.

A working fluid is circulated up through an inner coaxial lumen 56defined by an insulating coaxial layer 58 to a distal tip of the heattransfer element 50. The working fluid then traverses an outer coaxiallumen 50 in order to transfer heat to the exterior surface 52 of theheat transfer element 50. The inside structure of the heat transferelement 50 is similar to the exterior structure in order to induceturbulent flow of the working fluid.

FIG. 10 is a schematic representation of the invention being used tocool the brain of a patient. The selective organ hypothermia apparatusshown in FIG. 10 includes a working fluid supply 16, preferablysupplying a chilled liquid such as water, alcohol or a halogenatedhydrocarbon, a supply catheter 12 and the heat transfer element 14. Thesupply catheter 12 has a coaxial construction. An inner coaxial lumenwithin the supply catheter 12 receives coolant from the working fluidsupply 16. The coolant travels the length of the supply catheter 12 tothe heat transfer element 14 which serves as the cooling tip of thecatheter. At the distal end of the heat transfer element 14, the coolantexits the insulated interior lumen and traverses the length of the heattransfer element 14 in order to decrease the temperature of the heattransfer element 14. The coolant then traverses an outer lumen of thesupply catheter 12 so that it may be disposed of or recirculated. Thesupply catheter 12 is a flexible catheter having a diameter sufficientlysmall to allow its distal end to be inserted percutaneously into anaccessible artery such as the femoral artery of a patient as shown inFIG. 10. The supply catheter 12 is sufficiently long to allow the heattransfer element 14 at the distal end of the supply catheter 12 to bepassed through the vascular system of the patient and placed in theinternal carotid artery or other small artery. The method of insertingthe catheter into the patient and routing the heat transfer element 14into a selected artery is well known in the art.

Although the working fluid supply 16 is shown as an exemplary coolingdevice, other devices and working fluids may be used. For example, inorder to provide cooling, freon, perflourocarbon or saline may be used.

The heat transfer element of the present invention can absorb or provideover 75 Watts of heat to the blood stream and may absorb or provide asmuch a 100 Watts, 150 Watts, 170 Watts or more. For example, a heattransfer element with a diameter of 4 mm and a length of approximately10 cm using ordinary saline solution chilled so that the surfacetemperature of the heat transfer element is approximately 5° C. andpressurized at 2 atmospheres can absorb about 100 Watts of energy fromthe bloodstream. Smaller geometry heat transfer elements may bedeveloped for use with smaller organs which provide 60 Watts, 50 Watts,25 Watts or less of heat transfer.

The practice of the present invention is illustrated in the followingnon-limiting example.

EXEMPLE PROCEDURE

1. The patient is initially assessed, resuscitated, and stabilized.

2. The procedure is carried out in an angiography suite or surgicalsuite equipped with flouroscopy.

3. Because the catheter is placed into the common carotid artery, it isimportant to determine the presence of stenotic atheromatous lesions. Acarotid duplex (doppler/ultrasound) scan can quickly and non-invasivelymake this determinations. The ideal location for placement of thecatheter is in the left carotid so this may be scanned first. If diseaseis present, then the right carotid artery can be assessed. This test canbe used to detect the presence of proximal common carotid lesions byobserving the slope of the systolic upstroke and the shape of thepulsation. Although these lesions are rare, they could inhibit theplacement of the catheter. Examination of the peak blood flow velocitiesin the internal carotid can determine the presence of internal carotidartery lesions. Although the catheter is placed proximally to suchlesions, the catheter may exacerbate the compromised blood flow createdby these lesions. Peak systolic velocities greater that 130 cm/sec andpeak diastolic velocities>100 cm/sec in the internal indicate thepresence of at least 70% stenosis. Stenosis of 70% or more may warrantthe placement of a stent to open up the internal artery diameter.

4. The ultrasound can also be used to determine the vessel diameter andthe blood flow and the catheter with the appropriately sized heattransfer element could be selected.

5. After assessment of the arteries, the patients inguinal region issterilely prepped and infiltrated with lidocaine.

6. The femoral artery is cannulated and a guide wire may be inserted tothe desired carotid artery. Placement of the guide wire is confirmedwith flouroscopy.

7. An angiographic catheter can be fed over the wire and contrast mediainjected into the artery to further to assess the anatomy of thecarotid.

8. Alternatively, the femoral artery is cannulated and a 10-12.5 french(f) introducer sheath is placed.

9. A guide catheter is placed into the desired common carotid artery. Ifa guiding catheter is placed, it can be used to deliver contrast mediadirectly to further assess carotid anatomy.

10. A 10 f-12 f (3.3-4.0 mm) (approximate) cooling catheter issubsequently filled with saline and all air bubbles are removed.

11. The cooling catheter is placed into the carotid artery via theguiding catheter or over the guidewire. Placement is confirmed withflouroscopy.

12. Alternatively, the cooling catheter tip is shaped (angled or curvedapproximately 45 degrees), and the cooling catheter shaft has sufficientpushability and torqueability to be placed in the carotid without theaid of a guide wire or guide catheter.

13. The cooling catheter is connected to a pump circuit also filled withsaline and free from air bubbles. The pump circuit has a heat exchangesection that is immersed into a water bath and tubing that is connectedto a peristaltic pump. The water bath is chilled to approximately 0° C.

14. Cooling is initiated by starting the pump mechanism. The salinewithin the cooling catheter is circulated at 5 cc/sec. The salinetravels through the heat exchanger in the chilled water bath and iscooled to approximately 1° C.

15. It subsequently enters the cooling catheter where it is delivered tothe heat transfer element. The saline is warmed to approximately 5-7° C.as it travels along the inner lumen of the catheter shaft to the end ofthe heat transfer element.

16. The saline then flows back through the heat transfer element incontact with the inner metallic surface. The saline is further warmed inthe heat transfer element to 12-15° C., and in the process, heat isabsorbed from the blood cooling the blood to 30° C. to 32° C.

17. The chilled blood then goes on to chill the brain. It is estimatedthat 15-30 minutes will be required to cool the brain to 30 to 32° C.

18. The warmed saline travels back to down the outer lumen of thecatheter shaft and back to the chilled water bath were it is cooled to1° C.

19. The pressure drops along the length of the circuit are estimated tobe 2-3 atmospheres.

20. The cooling can be adjusted by increasing or decreasing the flowrate of the saline. Monitoring of the temperature drop of the salinealong the heat transfer element will allow the flow to be adjusted tomaintain the desired cooling effect.

21. The catheter is left in place to provide cooling for 12 to 24 hours.

22. If desired, warm saline can be circulated to promote warming of thebrain at the end of the therapeutic cooling period.

The design criteria described above for the heat transfer element, smalldiameter, high flexibility, use of highly conductive materials, andenhanced heat transfer rate through turbulent flow facilitate creationof a heat transfer element which successfully achieves selective organcooling. The combination of these elements are not addressed in theprior art. In addition, these prior art references do not identify amechanism for creating enhanced heat transfer rates through turbulentflow.

For example, U.S. Pat. No. 5,624,392 to Saab discloses a flexiblecoaxial catheter structure for transferring and removing heat from aremote body location, e.g., for cryosurgery or hyperthermic treatments.However, Saab discloses the use of an inflatable and collapsible ballooncatheter formed from an elastomeric material. The elastomeric materialis not highly conductive but instead the device relies on the thinningof the elastomeric walls in the inflated configuration in order tofacilitate heat transfer. Even if such a design could be reduced in bothdiameter and length such that it could be placed within the feedingartery of an organ, it would not provide a sufficiently high heattransfer rate to lower the temperature of an organ to a beneficiallevel. The device disclosed in Saab does not create turbulent flow witha turbulence intensity of 0.05 or greater.

Likewise, U.S. Pat. No. 5,486,208 to Ginsberg describes a catheter whichcan be placed into a blood vessel in order to raise or lower thetemperature of the entire body. The Ginsberg catheter is constructedfrom a flexible, non-conductive material. Several of the Ginsbergembodiments incorporate an inflatable and collapsible balloon structureat the distal end of the catheter. The balloon material has poor thermalconductivity and the device relies on increased surface area in theexpanded configuration in order to increase the heat transfer propertiesof the catheter. Ginsberg discloses the use of longitudinal, radial orspiral fins to further increase the surface area of the catheter. Evenwith the enhanced surface area design, the catheter disclosed inGinsberg would not provide the necessary heat transfer fororgan-selective hypothermia, even if the diameter and length of thedesign could be reduced to fit into the feeding artery of an organ. Asnoted above, simple techniques commonly used to induce a transition fromlaminar to turbulence flow, such as "tripping" the boundary layer do notwork in the arterial environment because the receptivity of the flow tothis forcing is extremely low. Thus, placing small wires or fins on thesurface of a device such as those disclosed in Ginsberg, does not createturbulent flow. The small fins or wires can create a local eddy ofturbulence, however, they do not create free stream turbulence. Inaddition, the device disclosed in Ginsburg does not create turbulentflow with a turbulence intensity of 0.05 or greater.

In addition to small size, it is also important that a catheter beflexible in order to be placed within the small feeding artery of anorgan. The Ginsberg and Saab devices are flexible. However, theflexibility of devices is achieved through the use of relativelynon-conductive, inherently flexible materials. These materials do notfacilitate good heat transfer properties in the devices. The Dato deviceis made from highly thermally conductive material but is not flexibleand, therefore, not suited for insertion into the feeding artery of anorgan. Further, the Dato device does not incorporate any surfacefeatures to promote turbulent kinetic energy, internally or externally.The device disclosed in Dato does not create turbulent flow with aturbulence intensity of 0.05 or greater.

Inducing selective organ hypothermia by intravascularly cooling theblood flow to that organ avoids many of the problems of the prior art.For example, because only a selected organ is cooled, complicationsassociated with total body hypothermia are avoided. Because the blood iscooled intravascularly, or in situ, problems associated with externalcirculation of the blood are eliminated. Also, only a single punctureand arterial vessel cannulation is required which may be performed at aneasily accessible artery such as the femoral, subclavian, or brachialarteries. By eliminating the use of a cold perfusate, problemsassociated with excessive fluid accumulation are avoided. In addition,rapid cooling to a precise temperature may be achieved. Further,treatment of a patient according to the invention is not cumbersome andthe patient may easily receive continued care during the heat transferprocess.

In addition, in some applications, it may be advantageous to attach astent to the distal end of the heat transfer element. The stent may beused to open arteries partially obstructed by atheromatous disease priorto initiation of heat transfer. Further, the device may be used todeliver drugs such blood clot dissolving compounds (i.e. tissueplasminogen activator) or neuroprotective agents (i.e. selectiveneurotransmitter inhibitors). In addition to therapeutic uses, thedevice may be used to destroy tissue such as through cryosurgery.

In addition to the detailed description above, a myriad of alternateembodiments will be readily discernible to one skilled in the art. Forexample, the bellows sections may be made of flexible conductive ornon-conductive material rather than metallic conductive material. Inaddition, a non-coaxial flow pattern may be used to transport theworking fluid through the supply catheter. The working fluid may flow upthe outer coaxial lumen and back down the inner coaxial lumen. In somecases, it may not be necessary to provide internal turbulence. In theembodiment above, turbulence was created using regular clockwise andcounterclockwise invaginations on the exterior surface of the heattransfer element. However, other external surface configurations maycreate turbulent flow patterns.

The invention may be embodied in other specific forms without departingfrom its spirit or essential characteristics. The described embodimentis to be considered in all respects only as illustrative and not asrestrictive and the scope of the invention is, therefore, indicated bythe appended claims rather than the foregoing description. All changeswhich come within the meaning and range of equivalency of the claims areto be embraced within their scope.

What is claimed is:
 1. A heat transfer device comprising:first andsecond elongated segments, each segment having a turbulence-inducingirregular exterior surface; a flexible articulating joint connecting thefirst and second elongated segments; and a tubular conduit disposedsubstantially coaxially within the first and second elongated,articulated segments, the conduit having an inner lumen for transportinga pressurized working fluid to a distal end of the elongated,articulated segments.
 2. The device of claim 1, wherein the first andsecond elongated, articulated segments each have an irregular interiorsurface to induce turbulence within a pressurized working fluid.
 3. Thedevice of claim 1, wherein irregularities on the turbulence-inducingexterior surface are shaped and sized to induce a turbulence intensitywithin a free stream blood flow greater than 0.05.
 4. The device ofclaim 1, wherein the turbulence-inducing exterior surfaces compriseinvaginations configured to have a depth which is greater than athickness of a boundary layer of blood which develops within an arterialflow.
 5. The device of claim 1, wherein the first and second elongated,articulated segments comprise alternating clockwise andcounter-clockwise invaginations.
 6. The device of claim 1, wherein thefirst and second elongated, articulated segments are formed from highlyconductive material.
 7. The device of claim 1 further comprising:acoaxial supply catheter having an inner catheter lumen coupled to theinner coaxial lumen within the first and second elongated, articulatedsegments; and a working fluid supply configured to dispense thepressurized working fluid and having an output coupled to the innercatheter lumen.
 8. The device of claim 7, wherein the working fluidsupply is configured to produce the pressurized working fluid at about0° C. and at a pressure below 5 atmospheres of pressure.
 9. The deviceof claim 1, further comprising:at least one additional elongated segmenthaving a turbulence-inducing irregular exterior surface; and at leastone additional flexible articulating joint connecting the at least oneadditional elongated segment to one of the first and second elongatedsegments.
 10. The device of claim 9, wherein the elongated, articulatedsegments comprise alternating clockwise and counter-clockwiseinvaginations.
 11. The device of claim 1, wherein theturbulence-inducing exterior surface is a clot-inhibiting surface. 12.The device of claim 1, further comprising a stent coupled to a distalend of the elongated, articulated segments.
 13. The device of claim 1,wherein the flexible joint comprises an axially compressible bellowssection.
 14. A method of treating an organ, comprising:inserting aflexible, conductive heat transfer element into a feeder artery from adistal location; and circulating a working fluid through the flexible,conductive heat transfer element to modify the temperature of the bloodin the feeder artery, thereby selectively modifying the temperature ofthe organ.
 15. The method of claim 14, further comprising regulating thetemperature and pressure of the working fluid to cause the flexible,conductive heat transfer element to absorb more than about 75 Watts ofheat.
 16. The method of claim 14, further comprising inducing turbulencewithin the free stream blood flow within the feeder artery.
 17. Themethod of claim 16, further comprising inducing blood turbulence with aturbulence intensity greater than 0.05 within the feeder artery.
 18. Themethod of claim 15, further comprising inducing blood turbulencethroughout the period of the cardiac cycle within the feeder artery. 19.The method of claim 16, further comprising inducing blood turbulencethroughout greater than 20% of the period of the cardiac cycle withinthe feeder artery.
 20. The method of claim 14, further comprisinginducing turbulent flow of the working fluid through the flexible,conductive heat transfer element.
 21. The method of claim 18, whereinpressure of the working fluid is maintained below 5 atmospheres ofpressure.
 22. The method of claim 18, wherein the working fluid isaqueous.
 23. A catheter for modifying the temperature of an organ,comprising:a catheter shaft having first and second lumens therein; aheat transfer tip adapted to transfer heat between blood surrounding theheat transfer tip and a working fluid circulated in through the firstlumen and out through the second lumen; and turbulence-inducingstructures on the exterior of the heat transfer tip, theturbulence-inducing structures being shaped and sized to induce freestream turbulence in blood flowing within a blood vessel; wherein theturbulence-inducing structures are shaped and sized to induce aturbulence intensity of at least about 0.05.
 24. A catheter formodifying the temperature of an organ, comprising:a catheter shafthaving first and second lumens therein; a heat transfer tip adapted totransfer heat between blood surrounding the heat transfer tip and aworking fluid circulated in through the first lumen and out through thesecond lumen; turbulence-inducing structures on the exterior of the heattransfer tip, the turbulence-inducing structures being shaped and sizedto induce free stream turbulence in blood flowing within a blood vessel;and turbulence-inducing structures on the interior of the heat transfertip, the turbulence-inducing structures being shaped and sized to induceturbulence within the working fluid.
 25. A catheter for modifying thetemperature of an organ, comprising:a catheter shaft having first andsecond lumens therein; a heat transfer tip adapted to transfer heatbetween blood surrounding the heat transfer tip and a working fluidcirculated in through the first lumen and out through the second lumen;and turbulence-inducing structures on the exterior of the heat transfertip, the turbulence-inducing structures being shaped and sized to inducefree stream turbulence in blood flowing within a blood vessel; whereinthe turbulence-inducing structures comprise invaginations which have adepth sufficient to disrupt the free stream blood flow in the bloodvessel.
 26. A catheter for modifying the temperature of an organ,comprising:a catheter shaft having first and second lumens therein; aheat transfer tip adapted to transfer heat between blood surrounding theheat transfer tip and a working fluid circulated in through the firstlumen and out through the second lumen; and turbulence-inducingstructures on the exterior of the heat transfer tip, theturbulence-inducing structures being shaped and sized to induce freestream turbulence in blood flowing within a blood vessel; wherein theturbulence-inducing structures comprise staggered protrusions which havea height sufficient to disrupt the free stream flow of blood in theblood vessel.
 27. A method of selectively inducing at least partialhypothermia in an organ of a patient, comprising:providing a catheterwith a flexible metallic heat transfer element disposed at a distal endthereof; inserting the catheter and heat transfer element into thevascular system of a patient to place at least a portion of the heattransfer element in a feeding artery of an organ; circulating a workingfluid through the catheter and through the heat transfer element tolower the temperature of the heat transfer element; and cooling blood inthe feeding artery by contact with the cooled heat transfer element. 28.A method of selectively inducing at least partial hypothermia in anorgan of a patient, comprising:providing a catheter with a flexiblemetallic heat transfer element disposed at a distal end thereof;inserting the catheter and heat transfer element into the vascularsystem of a patient to place at least a portion of the heat transferelement in a feeding artery of an organ; circulating a working fluidthrough the catheter and through the heat transfer element to lower thetemperature of the heat transfer element; cooling blood in the feedingartery by contact with the cooled heat transfer element; and cooling theorgan by flow of the cooled blood through the feeding artery whilemaintaining the core body temperature at a substantially constant level.29. A method of selectively inducing at least partial hypothermia in anorgan of a patient, comprising:providing a catheter with a flexiblemetallic heat transfer element disposed at a distal end thereof;inserting the catheter and heat transfer element into the vascularsystem of a patient to place at least a portion of the heat transferelement in a feeding artery of an organ; circulating a working fluidthrough the catheter and through the heat transfer element to lower thetemperature of the heat transfer element; cooling blood in the feedingartery by contact with the cooled heat transfer element; and cooling theorgan by flow of the cooled blood through the feeding artery such thatthe organ temperature decreases substantially prior to reduction of thecore body temperature.
 30. A method of selectively inducing at leastpartial hypothermia in an organ of a patient, comprising:providing acatheter with a flexible metallic heat transfer element disposed at adistal end thereof; inserting the catheter and heat transfer elementinto the vascular system of a patient to place at least a portion of theheat transfer element in a feeding artery of an organ; circulating aworking fluid through the catheter and through the heat transfer elementto lower the temperature of the heat transfer element, the working fluidbeing a liquid at temperatures in the range of about zero degreesCelsius to thirty-five degrees Celsius; cooling blood in the feedingartery by contact with the cooled heat transfer element; and cooling theorgan by flow of the cooled blood through the feeding artery whilemaintaining the core body temperature at a substantially constant level.31. A method of selectively inducing at least partial hypothermia in anorgan of a patient, comprising:providing a catheter with a flexiblemetallic heat transfer element disposed at a distal end thereof;inserting the catheter and heat transfer element into the vascularsystem of a patient to place at least a portion of the heat transferelement in a feeding artery of an organ; circulating a working fluidthrough the catheter and through the heat transfer element to lower thetemperature of the heat transfer element, the working fluid being aliquid at temperatures in the range of about zero degrees Celsius tothirty-five degrees Celsius; cooling blood in the feeding artery bycontact with the cooled heat transfer element; and cooling the organ byflow of the cooled blood through the feeding artery such that the organtemperature decreases substantially prior to reduction of the core bodytemperature.
 32. A method of selectively inducing at least partialhypothermia in an organ of a patient, comprising:providing a catheterwith a flexible metallic heat transfer element disposed at a distal endthereof, the flexible metallic heat transfer element having at least oneexternal flow-mixing feature disposed thereon; inserting the catheterand heat transfer element into the vascular system of a patient to placeat least a portion of the heat transfer element in a feeding artery ofan organ; circulating a working fluid through the catheter and throughthe heat transfer element to lower the temperature of the heat transferelement; cooling blood in the feeding artery by contact with the cooledheat transfer element, the cooling enhanced by the external flow-mixingfeature; and cooling the organ by flow of the cooled blood through thefeeding artery while maintaining the core body temperature at asubstantially constant level.
 33. A method of selectively inducing atleast partial hypothermia in an organ of a patient, comprising:providinga catheter with a flexible metallic heat transfer element disposed at adistal end thereof, the flexible metallic heat transfer element havingat least one external flow-mixing feature disposed thereon; insertingthe catheter and heat transfer element into the vascular system of apatient to place at least a portion of the heat transfer element in afeeding artery of an organ; circulating a working fluid through thecatheter and through the heat transfer element to lower the temperatureof the heat transfer element; cooling blood in the feeding artery bycontact with the cooled heat transfer element, the cooling enhanced bythe external flow-mixing feature; and cooling the organ by flow of thecooled blood through the feeding artery such that the organ temperaturedecreases substantially prior to reduction of the core body temperature.34. A method of selectively inducing at least partial hypothermia in anorgan of a patient, comprising:providing a catheter with a flexiblemetallic heat transfer element disposed at a distal end thereof, theflexible metallic heat transfer element having at least one externalflow-mixing feature disposed thereon; inserting the catheter and heattransfer element into the vascular system of a patient to place at leasta portion of the heat transfer element in a feeding artery of an organ;circulating a working fluid through the catheter and through the heattransfer element to lower the temperature of the heat transfer element,the working fluid being a liquid at temperatures in the range of aboutzero degrees Celsius to thirty-five degrees Celsius; and cooling bloodin the feeding artery by contact with the cooled heat transfer element,the cooling enhanced by the external flow-mixing feature.
 35. A methodof selectively inducing at least partial hypothermia in an organ of apatient, comprising:providing a catheter with a flexible metallic heattransfer element disposed at a distal end thereof, the flexible metallicheat transfer element having at least one external flow-mixing featuredisposed thereon; inserting the catheter and heat transfer element intothe vascular system of a patient to place at least a portion of the heattransfer element in a feeding artery of an organ; circulating a workingfluid through the catheter and through the heat transfer element tolower the temperature of the heat transfer element, the working fluidbeing a liquid at temperatures in the range of about zero degreesCelsius to thirty-five degrees Celsius; cooling blood in the feedingartery by contact with the cooled heat transfer element, the coolingenhanced by the external flow-mixing feature; and cooling the organ byflow of the cooled blood through the feeding artery while maintainingthe core body temperature at a substantially constant level.
 36. Amethod of selectively inducing at least partial hypothermia in an organof a patient, comprising:providing a catheter with a flexible metallicheat transfer element disposed at a distal end thereof, the flexiblemetallic heat transfer element having at least one external flow-mixingfeature disposed thereon; inserting the catheter and heat transferelement into the vascular system of a patient to place at least aportion of the heat transfer element in a feeding artery of an organ;circulating a working fluid through the catheter and through the heattransfer element to lower the temperature of the heat transfer element,the working fluid being a liquid at temperatures in the range of aboutzero degrees Celsius to thirty-five degrees Celsius; cooling blood inthe feeding artery by contact with the cooled heat transfer element, thecooling enhanced by the external flow-mixing feature; and cooling theorgan by flow of the cooled blood through the feeding artery such thatthe organ temperature decreases substantially prior to reduction of thecore body temperature.
 37. A selective organ heat transfer device,comprising:a flexible catheter capable of insertion to a selectedfeeding artery in the vascular system of a patient; a plurality of heattransfer segments attached to a distal end of said catheter, at leastone helical ridge and at least one helical groove formed on each of saidplurality of heat transfer segments, said helical groove having a depthcapable of inducing mixing in blood flow in the feeding artery, adjacentones of said plurality of heat transfer segments disposed in closeenough relation such that mixing arterial blood flow past one of saidplurality of heat transfer segments does not relaminarize prior topassing an adjacent one of said plurality of heat transfer segments; abellows disposed between each of said plurality of heat transfersegments; and an inner tube disposed within each of said plurality ofheat transfer segments and within each of said bellows, said inner tubebeing connected in fluid flow communication with an inner tube withinsaid catheter.
 38. A selective organ heat transfer device, comprising:aflexible catheter capable of insertion to a selected vessel in thevascular system of a patient; at least one heat transfer segmentattached to a distal end of said catheter, said heat transfer segmenthaving at least one mixing-inducing surface feature disposed thereon; abellows disposed adjacent and coaxial to said at least one heat transfersegment; and an inner tube disposed within said at least one heattransfer segment and within said bellows, said inner tube beingconnected in fluid flow communication with an inner tube within saidcatheter.